ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.205G>A (p.Glu69Lys)

dbSNP: rs397507511
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV000210038 SCV000265841 likely pathogenic not provided 2015-09-22 criteria provided, single submitter clinical testing
Centogene AG - the Rare Disease Company RCV001250211 SCV001424481 likely pathogenic Noonan syndrome 1 criteria provided, single submitter clinical testing
Ambry Genetics RCV002415881 SCV002725115 uncertain significance Cardiovascular phenotype 2017-03-10 criteria provided, single submitter clinical testing The p.E69K variant (also known as c.205G>A), located in coding exon 3 of the PTPN11 gene, results from a G to A substitution at nucleotide position 205. The glutamic acid at codon 69 is replaced by lysine, an amino acid with similar properties. This alteration has been described as an acquired somatic change in multiple cancer types, including: juvenile myelomonocytic leukemia (JMML), acute lymphoblastic leukemia (ALL), neuroblastoma, and astrocytoma (Loh ML et al. Blood, 2004 Mar;103:2325-31; Tartaglia M et al. Blood, 2004 Jul;104:307-13; Bentires-Alj M et al. Cancer Res., 2004 Dec;64:8816-20; Jones DT et al. Nat. Genet., 2013 Aug;45:927-32). In vivo functional studies have shown that this alteration results in increased and phosphatase activity compared to wild-type (Bentires-Alj M et al. Cancer Res., 2004 Dec;64:8816-20; Eminaga S et al. J. Biol. Chem., 2008 May;283:15328-38). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. There have been no reports of individuals clinically affected with Noonan syndrome or related disorders; since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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